The Candidate, Dr. Sylvester, is a post-doctoral fellow in Infectious Diseases and a doctoral candidate in the Graduate Training Program in Clinical Investigation at Johns Hopkins University. Through this award she seeks to become an independent investigator in patient-oriented research, with expertise in the area of Candida and candidiasis in compromised patient populations. Experts in clinical investigation, critical care, medical mycology, and biostatistics will mentor her. She will supplement her research activities and her knowledge of introductory biostatistics and epidemiology with advanced courses in clinical investigation, biostatistics and research ethics at the Bloomberg School of Public Health. To prepare for translational aspects of her future research, she will take courses in immunology, microbiology and molecular biology. Background - Candida is a deadly and increasingly common pathogen in critically ill patients. In certain patient populations, including critically ill surgical patients at Johns Hopkins, antifungal prophylaxis has been shown to prevent Candida infections. Antifungal prophylaxis has not been well studied in critically ill medical patients. The emergence of antimicrobial resistance among Candida species presents a major concern with regard to the widespread use of prophylaxis. Dr. Sylvester proposes to explore the ecology of Candida and the impact of antifungal prophylaxis in critically ill patients. Specific Aims. 1 ). To determine Candida species distribution and fluconazole susceptibilities in high-risk SICU patients and compare current species distribution and susceptibility data to data collected during a 1998-1999 randomized, double blind placebo-controlled trial of fluconazole prophylaxis in critically ill surgical patients at Johns Hopkins. 2). To determine Candida species distribution and fluconazole susceptibilities in high-risk MICU patients, to whom fluconazole prophylaxis is not given, and compare these data to data collected concurrently from high-risk SICU patients, to whom antifungal prophylaxis is routinely administered. 3). To evaluate, in a randomized, double blind, placebo-controlled trial, the effect of antifungal prophylaxis on the prevention of invasive Candida infection in high-risk, critically ill medical patients. Significance. The overall goals of this research are to define the ecology of Candida in critically ill patients, to define the impact of antifungal prophylaxis on this ecology, to assess differences in ecology and predictors of invasive infection in critically ill medical and surgical patients, and to develop a safe, effective strategy to prevent these often-fatal infections in critically ill medical patients.